Epidemiological, clinical and pathological characteristics of gastric neoplasms in the province of Cremona: the experience of the first population-based specialized gastric cancer registry in Italy.

BACKGROUND: The gastric cancer incidence rate differs widely across geographical areas. In Italy, in the province of Cremona the incidence is high, compared to the national situation. For this reason a specialized population-based registry was set up. METHODS: The collection encompasses all gastric cancers diagnosed in the three districts of the province since January 1, 2010. The main data sources were the pathological and Hospital Discharge Records and patient clinical charts. Only diagnoses of primary gastric cancer were considered. For each case the following variables were registered: personal data, medical history and symptoms at diagnosis; imaging assessments performed, details on surgery and other treatments received; genetic background and biomolecular characteristics; social and environmental factors. RESULTS: As of November 2017, 1087 cases were collected; of which 876, diagnosed up to December 2015, were analyzed. Male/female ratio was 1.4. The European Age-standardized Incidence Rate was 41.4 for males and 28.3 for females as compared to a national average of 33.3 and 17.0 respectively. Median age at diagnosis was 73 for male and 78 for female. Helicobacter Pylori infection was present in fewer than 20% of cases. HER-2 gene was amplified in about 25% of cases. Primary tumour location was the gastro-esophageal junction or cardia in 17.5% in males and 8.3% in females. The majority of cases (58.3%) were diagnosed at an advanced stage and overall only 41.2% underwent surgery. Median overall survival was 14.8 months for men and 18.5 for women. Age standardized 5-year relative survival was 31.4% for men and 40.5% for females. Neoadjuvant treatment was performed in fewer than 10% of patients who underwent surgery, and the rate of postoperative therapy adherence was low. DISCUSSION: This study shows a high gastric cancer incidence in the province of Cremona, with a geographical spread across different districts. Moreover, a high percentage of gastric cancers were detected at an advanced stage of disease and a low rate of 5-year relative survival was registered. Based on these findings, effective preventive interventional health strategies and screening procedures need to be implemented to reduce the impact of this pathology in this geographical area.

Prognostic factors associated with survival in a large cohort of gastric cancer patients resected over a decade at a single Italian center: the Cremona experience.

BACKGROUND: Incidence of gastric cancer (GC) shows different distribution in Italy, with higher incidence in the north and center. We retrospectively analyzed the clinical data of patients resected at the Hospital of Cremona between January 2007 and December 2016. Available clinical variables were linked with survival to identify possible prognostic factors. MATERIALS AND METHODS: Variables analyzed were age, sex, type of surgery, site, histology, invasion, nodal status, resection margins, grade, HER2 status, Helicobacter pylori infection (neo)adjuvant chemotherapy, adjuvant chemoradiotherapy, neutrophil-to-lymphocyte ratio, number of nodes removed and type of lymphadenectomy. Overall survival (OS) was estimated by the Kaplan-Meier method and differences between groups by the log-rank test. Data on OS were analyzed by Cox regression and the final model was obtained using the step-wise method. RESULTS: 379 patients were considered, out of which 195 were operated from 2007 to 2011 and 184 from 2012 to 2016. Median follow-up was 25.5 months, median OS 31.3 months and time to recurrence 23.2 months. D2 resection rate increased from 36% (period 2007-2011) to 74% in 2012-2016 (p = 0.01) with a higher mean number of nodes collected (20.98 for 2007-2011 and 23.53 for 2012-2016, p = 0.040). Only 37% of patients received a postoperative treatment. At multivariate analysis, variables associated with OS were age (p = 0.002), stage (p < 0.001), resection margins status (p < 0.001), adjuvant chemotherapy (p < 0.010) and tumor location (cardia vs non-cardia) (p = 0.029). CONCLUSIONS: Our analysis shows that completeness of resection and lower stage are strong predictors of long-term survival in GC, providing the rationale for adjuvant and neoadjuvant approaches (chemotherapy, radiotherapy or combined). Cardial GC has worse prognosis compared to distal cancers. TRIAL REGISTRATION NUMBER: Service evaluation number 256, protocol 16821/17, date 05 June 2017.

Tumor regression grade and survival after neoadjuvant treatment in gastro-esophageal cancer: A meta-analysis of 17 published studies.

INTRODUCTION: Major pathologic regression after neoadjuvant therapy is a strong and favorable prognostic factor in several types of cancer (breast, rectal and bladder). This information is less clear and has yet to be systematically evaluated in upper gastrointestinal tumors. We performed a meta-analysis to evaluate the prognostic impact of tumor regression after preoperative therapy on disease-free survival (DFS) and overall survival (OS) in gastro-esophageal cancer patients. METHODS: we searched for relevant articles in PubMed, SCOPUS, Web of Science, CINAHL, LILACS, Ovid, Cochrane Library, Google Scholar and Embase up to June 2, 2016. Data of tumor regression (complete or near-complete pathologic response) that independently correlated with OS and DFS in multivariate analysis were extracted, and the proper hazard ratios (HRs) with corresponding 95% confidence intervals (95% CIs) were pooled according to the random effect model. RESULTS: a total of 17 studies-which included 3145 patients-were considered in the final analysis. Major pathologic response was significantly related with better OS (HR 0.46, 95% CI 0.32-0.66, P < 0.001) and DFS (HR = 0.40, 95% CI 0.26-0.62, P < 0.001). Pathologic complete response (pCR) or major tumor regression were associated with the same degree of benefit in outcome compared to no or minimal pathologic regression, regardless of histology. CONCLUSION: major pathologic response is associated with a significant improvement in OS compared to no response or minor pathologic changes after neoadjuvant therapy in gastro-esophageal cancers. This should be considered a robust prognostic factor to guide postoperative treatment and follow-up.

Antiemetic activity of high doses of metoclopramide combined with methylprednisolone versus metoclopramide alone in cisplatin-treated cancer patients: a randomized double-blind trial of the Italian Oncology Group for Clinical Research.

We designed a multicenter, double-blind randomized study to determine the safety and antiemetic effectiveness of intravenous (IV) methylprednisolone (P) combined with high-dose IV metoclopramide (MTC) v MTC alone in 200 untreated cancer patients receiving cisplatin chemotherapy. One hundred eighty-five patients were evaluable for treatment efficacy. MTC plus P was significantly superior to MTC alone in reducing the number and length of vomiting episodes (P = .001 and P = .0008, respectively) and the maximal intensity of nausea (P = .0124 with a score system; P = .0155 with a linear analogue scale) and length of nausea (P = .0056). The subgroup with a major incidence of nausea and vomiting was women, especially young women, outpatients, and those treated with higher doses of cisplatin. Side effects were low and equally distributed between the two treatment groups. We conclude that MTC plus P has greater antiemetic activity than MTC alone in patients receiving cisplatin chemotherapy.

Double-blind, multicenter, randomized trial to compare the effect of two doses of adrenocorticotropic hormone versus placebo in controlling delayed emesis after high-dose cisplatin in adult patients with cancer.

PURPOSE: To compare, in a double-blind, placebo-controlled, randomized trial, the efficacy of two different doses of the depot formulation of adrenocorticotropic hormone (ACTH) in controlling delayed emesis after cisplatin. PATIENTS AND METHODS: One hundred fifty-two patients were enrolled onto the study. On day 1, all patients received cisplatin (60 to 120 mg/m2) and a combination of dexamethasone 20 mg plus ondansetron or metoclopramide to prevent acute emesis. On day 2 (24 hours after cisplatin administration), patients were randomized to receive placebo, or ACTH 1 mg intramuscularly (I.M.), or ACTH 2 mg I.M. plus one additional dose of 1 mg on day 4. Details of vomiting, nausea, and adverse effects were recorded daily for every 24-hour period from day 2 to day 6. In a subset of patients, serum cortisol levels were measured between 20 and 72 hours after cisplatin administration. RESULTS: One hundred fifty patients were assessable. Over the 5 days of the study, delayed vomiting occurred less frequently in the patients treated with ACTH 2 mg plus 1 mg than in those treated with ACTH 1 mg or placebo (28%, 38%, and 65%, respectively; P = .001). The greatest observed differences were seen on days 2 (24 to 48 hours; P = .01) and 3 (48 to 72 hours; P = .01). On days 4, 5, and 6 (96 to 144 hours), no significant differences were observed among the three arms. The severity of delayed emesis expressed as the mean number of emetic episodes per day was 0.48, 0.70, and 0.80, respectively (P = .002). Patients treated with the higher dose of ACTH had the least nausea on day 3 (P = .02) and day 4 (P = .03). Adrenal cortisol secretion rapidly increased after ACTH injection, but was suppressed for approximately 44 hours in the placebo group. Toxicity was mild and transient in all groups. CONCLUSION: ACTH reduces the incidence and severity of delayed vomiting and nausea after cisplatin. A dose of 2 mg 24 hours after cisplatin is better than one of 1 mg. Whether the activity of ACTH is mediated only by adrenal corticosteroids needs to be verified.

Dose-finding/phase II trial: bevacizumab, immunotherapy, and chemotherapy (BIC) in metastatic renal cell cancer (mRCC). Antitumor effects and variations of circulating T regulatory cells (Treg).

The aim of this study was to explore the efficacy and toxicities of a combined regimen of bevacizumab plus immunotherapy and chemotherapy (BIC) and the circulating T regulatory cells (Treg) in metastatic renal cell cancer (mRCC). Nephrectomized mRCC patients were enrolled into a multicenter single-arm dose-finding study with five escalated dose levels of chemotherapy with intravenous gemcitabine and 5-fluorouracil associated with fixed intravenous doses of bevacizumab, subcutaneous low doses of interleukin-2, and interferon-α-2a. An expanded cohort (phase II study) was treated at the recommended dose for additional safety and efficacy information according to minimax Simon two-stage design. Blood samples for Treg were collected and evaluated by fluorescence-activated cell sorting (FACS) analysis on cycle 1. Fifty-one patients were entered to receive one of five dose levels. Median age was 58 years (male 67 %, pretreated 49 %): 15 patients were low risk according to Memorial Sloan-Kettering Cancer Center (MSKCC) criteria, while 27 and nine were respectively intermediate- and high-risk patients. More frequent grade 3 and 4 toxicities included nonfebrile neutropenia, thrombocytopenia, and fever. Among patients evaluable for response (49), 29.5 % had partial response and 37 % stable disease. Overall median time to progression and median overall survival were 8.8 and 22.67 months, respectively. We observed a rapid increase in the percentage of Treg after immunotherapy and a reduction after bevacizumab only in patient who obtained a partial response or stable disease. The BIC was feasible, well tolerated, and shown interesting activity. Further studies are needed to explore if Treg could have a role in clinical response in mRCC treated with bevacizumab.

Epirubicin versus CMF as adjuvant therapy for stage I and II breast cancer: a prospective randomised study.

We compared a relatively short regimen of monochemotherapy with epirubicin versus polychemotherapy with CMF (cyclophosphamide, methotrexate, 5-fluorouracil) as adjuvant treatment for stage I and II breast cancer patients. 348 patients with oestrogen receptor negative (ER-) node negative and ER- or ER+ node-positive with <10 nodes were accrued. CMF was given intravenously (i.v.) on days 1 and 8, every 4 weeks, for six courses; epirubicin was given weekly for 4 months. Postmenopausal patients received tamoxifen for 3 years. The primary endpoints were overall survival (OS), relapse-free survival (RFS) and event-free survival (EFS). Outcome evaluation was performed both in eligible patients and in all randomised patients according to the intention-to-treat principle. 8 randomised patients were considered ineligible. At a median follow-up of 8 years, there was no difference in OS (Hazard Ratio (HR)=1.11, 95% Confidence Interval (CI): 0.77-1.61, P=0.58), EFS (HR=1.14, 95% CI: 0.78-1.64, P=0.48), and RFS (HR=1.14, 95% CI: 0.8-1.64, P=0.48) between the two arms for all of the patients. At 8 years, the RFS percentages (+/-Standard Error (S.E.)) were 65.4% (+/-4%) in the CMF arm and 62.7% (+/-4%) in the epirubicin arm; for EFS these were 64.2% (+/-4%) for CMF and 60.8% (+/-4%) for epirubicin, respectively. A significant difference in RFS (P=0.015) was observed in patients with 4-9 positive nodes in favour of the CMF arm. Toxicity in the two arms was superimposable except for more frequent grade 3 alopecia in the epirubicin-treated patients (P=0.001). Overall, at a median follow-up of 8 years, there were no differences between the two arms in terms of OS, EFS and RFS.

Treatment of metastatic malignant melanoma with dacarbazine plus tamoxifen, or vindesine plus tamoxifen: a prospective randomized study.

This study aimed to verify whether the advantage in terms of response rate and survival of dacarbazine plus tamoxifen over dacarbazine alone in metastatic malignant melanoma reported in a previous randomized trial was due to a specific interaction of dacarbazine with tamoxifen. A total of 125 patients with locoregional or disseminated malignant melanoma were randomized to receive dacarbazine (250 mg/m(2) days 1-5 every 3 weeks) plus tamoxifen (arm A) or vindesine (3 mg/m(2) every week for 6 weeks, then every 2 weeks) plus tamoxifen (arm B). Of the 125 randomized patients, 57 and 59 were evaluable in arm A and B, respectively. The complete response rates were the same (2% versus 2%) and the complete plus partial response rates were similar (11% versus 14%) in the two groups. There was no significant difference in survival. Neither response or survival correlated with gender. In conclusion, when combined with tamoxifen, dacarbazine does not have a specific effect on response or survival compared with vindesine. The lower response rate to dacarbazine plus tamoxifen (11%) than that reported in the previous trial (28%) might be explained by actual differences in patient and/or participating centre accrual characteristics in the presence of apparently identical eligibility criteria.

High-dose folinic acid and 5-fluorouracil alone or combined with hydroxyurea in advanced colorectal cancer: a randomized trial of the Italian Oncology Group for Clinical Research.

Patients with histologically confirmed advanced colorectal cancer were randomized to receive folinic acid (FA; 500 mg/mq in 2-hour intravenous infusion) and 5-fluorouracil (5FU; 600 mg/mq given as an intravenous bolus 1 hour after FA), beginning every week for 6 weeks, followed by a 2-week rest period, either without hydroxyurea (HU, arm A) or with HU (35 mg/kg per day) given orally in three administrations (every 8 hours) starting 6 hours after 5FU administration (arm B). Six weekly doses were considered one course. One hundred eighty-two patients were randomized in this trial and 162 (89%) were evaluable for response: 81 patients in arm A and 81 patients in arm B. Objective response was observed in 18 (one complete response and 17 partial responses) of 81 evaluable patients (22%; 95% confidence interval, 13-31%) in arm A, and 24 (nine complete responses and 15 partial responses) of 81 patients (30%; 95% confidence interval, 20-40%) in arm B. There was no difference in terms of median time to progression and median survival. Gastrointestinal toxicity was the most frequently observed toxicity in both arms. The double modulation of 5FU, FA plus HU does not appear to be better than the classic 5FU plus FA schedule. This trial confirms that 5FU and FA reached a plateau of 20% to 30%.

Mature results of a prospective randomized trial comparing a three-weekly with an accelerated weekly schedule of cisplatin in advanced ovarian carcinoma.

In a retrospective analysis of a series of clinical trials by Levin and Hryniuk in 1987, the average relative dose intensity of first-line chemotherapy for advanced ovarian cancer correlated significantly with clinical response and survival, and cisplatin was the only drug for which the outcome correlated with the individual drug relative dose intensity. There was a need to test whether and to what extent this evidence would be confirmed in a prospective evaluation. In this study 101 patients with advanced ovarian carcinoma were randomized to receive the same total dose of cisplatin but at the conventional 3-weekly schedule (CTWS) (100 mg/m2 every 3 weeks for six cycles) (51 patients) or at an experimental accelerated weekly schedule (AWS) (100 mg/m2 every week for two triplets of three cycles separated by a 5-week interval) (50 patients). To benefit from a multidrug regimen at the same extent, patients in both arms sequentially received four cycles of doxorubicin and cyclophosphamide. The median follow-up period of this study is 9.7 years. In 42 and 40 patients of the two arms having evaluable response, the clinical complete response rates to cisplatin were 14% and 22% and the complete plus partial response rates were 48% and 55% in the CTWS and in the AWS arm, respectively. These differences were not statistically significant. However, the survival curves were similar during the first 2 years but clearly diverged thereafter in favor of the AWS arm (p = 0.07). At 5 years, 12% and 30% of the patients were still alive in the CTWS and in the AWS arm, respectively. Hematologic toxicity was not relevant in either arm of the study. Nonhematologic toxicity, especially ototoxicity, was substantial and significantly higher in the AWS arm. Although statistically nonsignificant, this AWS regimen of cisplatin is associated with long-term better survival compared to the CTWS regimen in advanced ovarian carcinoma. This accelerated approach administering cisplatin should be further investigated, especially in patients with low residual disease after primary surgery.

Aminoglutethimide in advanced breast cancer.

From July 1980 to June 1983, 61 postmenopausal women with progressive metastatic breast cancer were treated with aminoglutethimide, 250 mg 4 times daily, plus cortisone acetate, 25 mg twice daily. Of 51 evaluable patients, an objective remission was observed in 22 (43%) (partial remission in 19, complete in 3), stable disease in 14 (27%), and progressive disease in 15 (30%). The median duration of response was 60 weeks (range 12+; 94+). The response rate was higher when the dominant disease site was soft tissue (50%) or bone (56%) rather than viscera (29%). Side effects were common but usually slight and transient. Somnolence (69%), dizziness (41%), nausea (35%) and skin rash (27%) were the most frequent. Serum levels of gamma-GT, alkaline phosphatase and total cholesterol rose during aminoglutethimide treatment, whereas levels of uric acid and indirect bilirubin decreased. Aminoglutethimide plus cortisone acetate appears to be an active and relatively safe treatment in advanced breast cancer and may be recommended as second-line endocrine treatment.

Bone marrow biopsy in the staging of small cell lung cancer.

From April 1982 to December 1987, 71 patients with small cell lung cancer entered a randomized clinical trial, and underwent bone marrow biopsy (BMB) as part of staging procedures. We identified 8 patients (11%) with bone marrow metastases, 6 with extensive disease independently of BMB, and 2 with extensive disease on the basis of the BMB only. BMB determined a change in the stage in only 3% (2/71) of the cases. No differences were found in the hematological parameters of the patients with or without bone marrow metastases. The median survival of the patients with bone marrow involvement was the same (41 weeks) as those with extensive disease but without bone marrow involvement. We conclude that unilateral BMB without aspiration detects a substantial proportion of bone marrow metastases in patients with extensive disease. This fact does not worsen the prognosis. A small proportion of patients with apparently limited disease has bone marrow involvement. The technique therefore contributes, to a small extent, to the definition of the clinical stage of the disease. However, bone marrow involvement is an important data of natural history, and therefore new methods to better assess this peculiar site of the disease are needed.

Lonidamine in advanced colorectal cancer: a phase II study of the Italian Oncology Group for Clinical Research (GOIRC).

Twenty-one patients with metastatic colorectal adenocarcinoma, all previously treated with chemotherapy for metastatic disease, were treated with lonidamine (LDN). The major toxicity encountered was muscular (myalgias in 48%) and gastro-intestinal (nausea and/or vomiting in 52%). Other toxicities included abdominal pain, somnolence, fever, arthralgia and ototoxicity. In the 14 patients evaluable for response we observed no complete or partial remission, 8 stable disease and 6 progressive disease. LND has no clinically worthwhile activity against colorectal carcinoma refractory to conventional chemotherapy.

[Neoadjuvant chemotherapy in advanced-stage bladder carcinoma. A randomized prospective study comparing MVAC and MVEEC]. / Chemioterapia neoadiuvante nel carcinoma vescicale in stadio avanzato. Studio prospettico randomizzato tra la combinazione MVAC ed MVEEC.

The Authors report the results with combination of cisplatin, methotrexate, vinblastine with adriamycin or epidoxorubicin (MVAC v MVEEC), in the neoadjuvant treatment of muscle-infiltrating bladder cancer (T2-4NO-1MO), before cystectomy. MVAC has been used in 29 patients and MVEEC in 25, who met eligibility criteria. Results from this prospective randomised trial show that MVAC and MVEEC can produce clinical and pathologic down-staging in 40-50% of cases: cCR+cPR are 15/28 (54%), pCR+pPR are 11/25 (44%). The survival duration of "pathologic" responders has been significantly longer than that of no responders (median no achieved at 200 weeks v 124 weeks for "pathologic" no responders). We conclude that neoadjuvant chemotherapy with MVAC or MVEEC select the more responsive patients, who have a longer survival.

[Polymyalgia rheumatica and malignant neoplasms. A report of 3 cases]. / Polimialgia reumatica e neoplasie maligne. Descrizione di tre casi.

Polymyalgia rheumatica (PMR) is an inflammatory disease which mainly affects elderly patients and is highly responsive to steroid therapy. PMR can be associated with giant cell arteritis and, less frequently, with malignancy. The authors describe three cases of paraneoplastic PMR. In one patient PMR has been the initial manifestation of a B-cell non-Hodgkin lymphoma, in two of a malignant neoplasm of the gastrointestinal system. In two patients the response to steroid therapy was documented. A careful clinical evaluation and a long term follow-up is needed before considering PMR an idiopathic disease.

A prospective observational study to evaluate G-CSF usage in patients with solid tumors receiving myelosuppressive chemotherapy in Italian clinical oncology practice.

Febrile neutropenia (FN) is a severe dose-limiting side effect of myelosuppressive chemotherapy in patients with solid tumors. Clinical practice guidelines recommend primary prophylaxis with G-CSF in patients with an overall ≥ 20 % risk of FN. AIOM Italian guidelines recommend starting G-CSF within 24-72 h after chemotherapy; for daily G-CSF, administration should continue until the absolute neutrophil count (ANC) is 1 × 10(9)/L post-nadir and should not be terminated after ANC increase in the early days of administration. The aim of this study was to assess guideline adherence in oncology practice in Italy. In this multicenter, prospective, observational study, patients were enrolled at the first G-CSF use in any cycle and were followed for two subsequent cycles (or until the end of chemotherapy if less than two additional cycles). Primary objective was to explore G-CSF use in Italian clinical practice; therefore, data were collected on the G-CSF type, timing of administration, and number of doses. 512 eligible patients were enrolled (median age, 62). The most common tumor types were breast (36 %), lung (18 %), and colorectal (13 %). A total of 1,164 G-CSF cycles (daily G-CSF, 718; pegfilgrastim, 446) were observed. Daily G-CSF was administered later than 72 h after chemotherapy in 42 % of cycles, and the median [range] number of doses was four [1, 10]. Pegfilgrastim was administered later than 72 h in 8 % of cycles. G-CSF prophylaxis in Italy is frequently administered in a manner which is not supported by evidence-based guidelines. As this practice may lead to poor outcomes, educational initiatives are recommended.

Lack of KRAS, NRAS, BRAF and TP53 mutations improves outcome of elderly metastatic colorectal cancer patients treated with cetuximab, oxaliplatin and UFT.

There is conflicting evidence on the predictive role of KRAS status when cetuximab is added to oxaliplatin-based regimens. This study investigated the impact of KRAS, NRAS, BRAF, PI3KCA and TP53 status on outcome of elderly metastatic colorectal cancer patients enrolled in TEGAFOX-E (cetuximab, oxaliplatin and oral uracil/ftorafur--UFT) phase II study. Twenty-eight patients were enrolled and all were evaluable for safety and activity. Twenty-three specimens were analysed for KRAS, BRAF, NRAS, PI3KCA and TP53 mutational status by means of polymerase chain reaction and correlated with objective response, progression-free survival and overall survival. An evident increase of response rate was noted in KRAS/NRAS wild-type cases (70 versus 33%, P = 0.198). KRAS/NRAS wild-type status showed an independent association with a longer progression-free survival (44 versus 9 weeks, P = 0.009). Considering the combined assessment of BRAF, KRAS/NRAS and TP53, a trend towards an increase of response rate was noted in patients without mutations (83 versus 33%, P = 0.063). Moreover, patients with all wild-type genes had significantly longer progression-free survival than patients with any mutation (48 versus 10 weeks, P = 0.007). As a single biomarker, only KRAS/NRAS proteins maintained an independent value for outcome prediction. Patients with KRAS/NRAS, BRAF and TP53 wild-type tumours could derive the maximal benefits from treatment with cetuximab, oxaliplatin and UFT.

The Breast Avastin Trial: phase II study of bevacizumab maintenance therapy after induction chemotherapy with docetaxel and capecitabine for the first-line treatment of patients with locally recurrent or metastatic breast cancer.

BACKGROUND: Therapeutic approach for patients with metastatic breast cancer (MBC) is still controversial. This study was conducted to assess the efficacy and safety of bevacizumab in combination with docetaxel plus capecitabine as first-line treatment for MBC. The feasibility of bevacizumab maintenance therapy in this setting was also evaluated. PATIENTS AND METHODS: In this single-arm, multicenter phase II study, patients received bevacizumab 15 mg/kg and docetaxel 60 mg/m(2) on day 1, plus capecitabine 900 mg/m(2) twice daily on days 1-14 every 21 days. Treatment was administered for up to 6 cycles, then bevacizumab continued until progressive disease. The primary end point was progression-free survival (PFS); secondary end points were tumor response rate, overall survival, and toxicity. RESULTS: Seventy-nine eligible patients were treated with bevacizumab in combination with docetaxel plus capecitabine. The overall response rate was 61 %, with a complete response rate of 8 % and a median duration of response of 10 months. At a median follow-up of 28 months, the median PFS was 11 months. Fifty-two (65 %) patients received bevacizumab maintenance therapy for a median duration of 7 months (range 1 to 33+). Neutropenia was the most common grade 3-4 toxicity (28.1 % of patients), and two fatal adverse events occurred (septic shock and gastrointestinal perforation). CONCLUSIONS: Bevacizumab in combination with docetaxel and capecitabine demonstrates significant activity and quite acceptable toxicity profile as first-line treatment of MBC. Subsequent maintenance therapy with bevacizumab is feasible for a long period of stable disease. Results deserve confirmation.

Double-blind, randomized trial for the control of delayed emesis in patients receiving cisplatin: comparison of placebo vs. adrenocorticotropic hormone (ACTH).

Delayed nausea and vomiting is a significant problem for the majority of patients receiving cisplatin. We designed a double-blind randomized study comparing the effects of ACTH and placebo on delayed emesis. Sixty-four adult cancer patients entered this trial; all received a chemotherapy regimen containing cisplatin (greater than or equal to 60 mg/m2) and a combination of metoclopramide and dexamethasone for the control of acute emesis during the period from 0 to 24 h after cisplatin (day 1). Twenty-four hours after cisplatin (day 2) they were randomized to receive 1 mg of ACTH i.m. in its long-acting form, or placebo in an identical vial. All patients were asked to keep a daily record of the incidence and severity of delayed vomiting and nausea for each of the five consecutive 24-h periods after cisplatin administration. Sixty patients were evaluable. The percentages of patients experiencing vomiting in the ACTH and placebo arms were, respectively, 17% vs. 43% on day 2 (24-48 h after cisplatin) (P = 0.04), 13% vs. 40% on day 3 (48-72 h) (P = 0.04), 20% vs. 34% on day 4 (72-96 h), and 20% vs. 30% on day 5 (96-120 h). During the entire 5-day study period, 33% of the patients in the ACTH group experienced delayed vomiting as opposed to 57% in the placebo arm (P = 0.11).(ABSTRACT TRUNCATED AT 250 WORDS)